HPS1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: biogenesis of lysosomal organelles complex 3 subunit 1
  • A component of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) complex along with HPS4
  • BLOC-3 complex plays a role in the biogenesis of lysosomes and lysosome-related organelles (LROs) such as melanosomes and platelet dense granules
  • Lysosomes are cytoplasmic organelles that serve as a major degradative compartment in eukaryotes
  • LROs have similar features to lysosomes but have distinct morphology, composition and/or function
Clinical phenotype
(OMIM phenotype no.)
  • Hermansky-Pudlak syndrome 1 (#203300)
  • Autosomal recessive
Ocular features
  • Albinism
  • Intra- and interfamilial variability in disease severity
Systemic features
  • Skin and hair depigmentation
  • Bleeding diathesis (easy/prolonged bleeding, easy bruising, prolonged/heavy menorrhagia, epistaxis)
  • At risk of developing pulmonary fibrosis (onset usually during early 30s) and granulomatous colitis
Key investigations
  • Orthoptic assessment and refraction
  • OCT to detect foveal hypoplasia
  • Visual evoked potentials to detect evidence of chiasmal misrouting
  • Eye movement recordings
  • Systemic assessment with a pediatrician, haematologists and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (albinism)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under research
Further information

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Additional information

Hermansky-Pudlak syndrome (HPS) patients with BLOC-3 defects (HPS1 or HPS4) have more severe ocular and systemic phenotypes compared to those with BLOC-2 defects (HPS3, HPS5 and HPS6).[2] HPS is very common among Puerto Ricans, especially in the north-western part of the country with an incidence of roughly 1:1,800.[3] All HPS patients from this part of the country are homozygous for the 16-base pair (bp) duplication in exon 15 of the HPS1 gene due to a founder mutation.[3-5] 

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  1.  Kornfeld S, Mellman I. The biogenesis of lysosomes. Annu Rev Cell Biol. 1989;5:483-525
  2.  Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359-386
  3.  Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, et al. Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico. J Invest Dermatol. 2006;126(1):85-90
  4.  Gahl WA, Brantly M, Kaiser-Kupfer MI, et al. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998;338(18):1258-1264
  5.  Toro J, Turner M, Gahl WA. Dermatologic manifestations of Hermansky-Pudlak syndrome in patients with and without a 16-base pair duplication in the HPS1 gene. Arch Dermatol. 1999;135(7):774-780
  6.  Carmona-Rivera C, Simeonov DR, Cardillo ND, Gahl WA, Cadilla CL. A divalent interaction between HPS1 and HPS4 is required for the formation of the biogenesis of lysosome-related organelle complex-3 (BLOC-3). Biochim Biophys Acta. 2013;1833(3):468-478
  7.  Ito S, Suzuki T, Inagaki K, et al. High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. J Invest Dermatol. 2005;125(4):715-720

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Updated on November 30, 2020
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